Early Data Indicate Erlotinib Controls Advanced NSCLC in Elderly Patients, Phase II Trial Shows

March 1, 2005

This special “annual highlights” supplement to Oncology News International is acompilation of major advances in the management of lung cancer during 2004, asreported in ONI. Guest editor Dr. Roy Herbst discusses these advances in clinicalmanagement, with a focus on developments in adjuvant therapy for early disease,targeted therapy, and new chemotherapy findings.

BOSTON-Erlotinib (Tarceva)produced a disease control rate of63.2% in elderly patients with previouslyuntreated advanced non-small-cell lung cancer (NSCLC), andat a median follow up of 6 months, 33of the 38 study patients were still alive.Bruce E. Johnson, MD, of Dana-Farber Cancer Institute in Boston presentedpreliminary phase II data (abstract7080) at the 40th annualmeeting of the American Society ofClinical Oncology."Erlotinib demonstrated encouragingantitumor activity in patientsover age 70 who had previouslyuntreated, advanced NSCLC. Responseswere observed in advanceddisease and in bronchoalveolar carcinoma[BAC]," Dr. Johnson said.Elderly patients are more vulnerableto chemotherapy-related toxicitythan younger patients. Dr. Johnsonexplained that erlotinib was an attractivecandidate in this setting becauseof its activity and generally low sideeffectprofile in the treatment ofpatients who have failed prior chemotherapy.Nearly All Were SmokersThis ongoing single center phaseII study is enrolling patients at least70 years of age who are chemotherapy-naive and have stage IIIB (withmalignant effusion) or stage IVNSCLC and performance status (PS)of 0 to 2. Patients are treated with oralerlotinib 150 mg/d until evidence ofdisease progression or toxicity.The primary study endpoint ismedian survival. Secondary endpointsinclude response rate, quality of life,changes in fluorodeoxyglucosepositronemission tomography (FDGPET) imaging, and analysis of theEGFR signaling pathway from pretreatmenttumor specimens.Dr. Johnson reported data for 38patients who were evaluable for toxicityand response at the time of thispresentation. Median age was 76 years, with a range of 70 to 86. Most patients(28/38) were PS 1. Nearly all (30/38)were former smokers, and two werecurrent smokers.Fifty-six percent of the patients hadadenocarcinomas; 14% had squamouscell carcinomas; 11% had adenocarcinomaswith BAC features; 11% hadBAC; 11% had unclassified NSCLC and 2% had large cell carcinomas.Five patients (13.1%) had partialresponses with a median duration of8.0 months, and 19 (50%) had diseasestabilization with a median durationof 3.5 months. "Survival andFDG-PET imaging outcomes are tooearly to evaluate," Dr. Johnson said.Rash affected 77% of patients butwas grade 1 or 2 in 92% of those affected."All of the responding patientsdeveloped rash," Dr. Johnson noted.Grade 1 or 2 diarrhea developed in61% of patients. Grade 3 or worsetoxicities included pneumonitis(6.5%) and lacrimation (3.2%). Dr.Johnson reported that one patientdied from drug toxicity (pneumonitis).Three patients (8.5%) were dosereduced owing to toxicity, and threepatients discontinued treatment."Erlotinib appears to be well toleratedand demonstrates encouragingactivity in patients at least 70 years ofage with previously untreated advancedNSCLC. Accrual is continuing to 60patients," Dr. Johnson said.